Although progress has been made in describing a variety of secretory processes and some insights have been made regarding the mechanisms involved in the secretory process, the cellular control mechanisms and molecular events involved in exocrine secretion are still poorly understood. A better understanding of the secretory process will provide needed information if we are to better understand the possible dysfunction of exocrine tissue in disease; such as in cystic fibrosis. Thus, we are proposing to study certain aspects of fluid secretion in rat submandibular tissue. Once having gained additional insight in the molecular events involved, we eventually plan to study human tissue, salivary cells from normal patients and from patients with cystic fibrosis. In particular, we are proposing to study the role of calcium and cyclic GMP in the production of the primary secretory fluid. Therefore, we intend: (1) characterize and localize the calcium-dependent endogenous protein phosphorylation events; (2) use certain pharmacological agents that are known to interfere with normal calmodulin function, trifluoperazine and chloropromazine, to study their effects on cellular protein phosphorylation and on fluid secretion via assaying K release, Na,K-ATPase activation, and calcium flux. Furthermore, we plan to: (1) determine the effects of cholinergic and adrenergic stimulation on the level and cellular distribution of cyclic GMP; (2) characterize and localize the cyclic GMP-dependent protein kinase; (3) characterize and localize the endogenous protein substrates for cGMP-PK; and (4) use cyclic GMP analogs to study the interrelationship between cyclic GMP metabolism, cyclic GMP-dependent protein phosphorylation, Na,K-ATPase activation and fluid secretion. The data should provide important fundamental information regarding exocrine gland secretion and may provide important data for improving general oral health.